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BIG PHYSICS, BIG QUESTIONS –

First timeline of a cancer tracks tumours from origin to spread

Tracking cancer’s spread could give us clues about how to treat it

Steve Gschmeissner/Science Photo Library

By Andy Coghlan

There’s rarely a silver lining to a cancer diagnosis. But one man’s illness has led to the first precise tracing of a cancer’s evolution. Knowing the exact time at which a particular tumour developed in the patient’s body allowed scientists to create a timeline for how his cancer evolved from a few cells, all the way through to the tumours that caused his eventual death.

The study provides clues about what makes some cancers spread rapidly, and may in the future help doctors estimate how a tumour might respond to therapies.

The analysis was carried out on a man diagnosed with bowel cancer in 2008, which later metastasised, spreading into other areas of his body. When the primary cancer was surgically removed, Nicola Valeri at the Institute of Cancer Research in London, discovered a nodule in the man’s lung. He suspected this might also be cancerous but decided to keep an eye on it before performing any further surgery.

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In 2011, a piece of the nodule was extracted using a needle and analysed, revealing that it was a secondary tumour, which was subsequently removed.

But the biopsy left a legacy: as doctors withdrew the needle, it left behind a trail of cells from the tumour – an unfortunate but rare side effect of the procedure. These cells subsequently turned into another secondary tumour in the patient’s chest wall

This tumour was not discovered until two years later, in 2013. It occupied the precise track from where the needle had been inserted, and so must have originated on the day of the biopsy.

This rare turn of events provided Valeri and his colleagues with a kind of stopwatch – an exact point in time when a few cells began their two year evolution into a metastatic tumour.

They used this timestamp, alongside a genetic analysis of all the tumours the man developed before dying – including the primary bowel tumour – to work out how the cancer had progressed over his lifetime.

Knowing the exact time when the rare chest wall tumour was born, they could study how many mutations it had developed by the time they re-examined it two years down the line. This gave them information about the rate of change, which they could then extrapolate and use to follow the progression of the disease back in time to its origins.

Back in time

The analysis showed that the primary colon cancer had actually emerged five to eight years before it was diagnosed. Around a year after it emerged, this primary cancer metastasised and travelled to the lung and the thyroid. The thyroid tumour was eventually discovered in 2012. The patient died in 2015 from new metastasis in his kidneys.

Valeri says that the biggest surprise from the analysis was that the cancer had spread so quickly from the bowel to the lung and thyroid, yet all three of these tumours remained dormant for many years, instead of continuing to spread and grow. “It suggests that sometimes, there’s a large time window to make diagnosis early and disrupt metastatic spread,” he says. “It means there might be periods of years where we could intervene.”

“Metastases caused by biopsy needles are rare, but in this case it meant the scientists could use the situation to develop a personal roadmap of this patient’s bowel cancer development,” says Justine Alford, senior science information officer at Cancer Research UK. “Through this unique research journey, the study reveals new and surprising insights into the timings of bowel cancer spread, demonstrating the disease’s complexity and highlighting how much more there is to discover.”

Strange turn of events

The analysis revealed important clues about why the cancer spread so fast, then settled for years before becoming aggressive. Although a mutation in a gene known to promote the spread of cancerous cells occurred early on, this did not appear to effect the development of the subsequent metastases. These tumours also failed to evolve the large genetic alterations that make cancers most aggressive – such as duplications or losses of entire chromosomes.

“The surprise for me was how fast metastasis happened, and then how indolent it was after that point,” says Carlo Maley of Arizona State University, in Tempe, who specialises in cancer evolution and who contributed to the analysis. “I usually think of metastasis as the start of a runaway process that kills us.”

“Studies like these and the tools they use will be critical in the future management of cancer,” says Maley. He says such tools will allow us to judge how fast a tumour is evolving and use that to predict its response to therapies.